Arginine rich protamines peptides (30-50 amino acids) spontaneously assemble DNA into extended, close-packed (<1 nm surface-to-surface separation), liquid crystalline arrays that are suitable for characterization by x-ray scattering. Reconstituted protamine-DNA assemblies and sperm nuclei give very similar x-ray scattering profiles. Using synthetic peptides we were able to determine that (1) protamines use arginine almost exclusively over lysine to condense DNA because lysine rich peptides pack DNA very poorly in comparison and (2) the DNA packing density in salmon sperm nuclei is completely determined by the 21 arginines and 33% neutral amino acids of salmon protamine. Assisted reproductive technologies (ART) routinely use density fractionation of sperm to ensure only high quality sperm are used to artificially inseminate ova. Salmon sperm nuclei can be fractionated on a sucrose density gradient. The denser fraction has a narrow distribution of DNA interhelical distances with a peak at 0.9 nm surface-to-surface separation. The less dense fraction has the same peak spacing, but the scattering profile is skewed toward larger separations indicating a DNA subpopulation that is more loosely packed. Adding excess protamine to the light fraction recovers the scattering profile of the denser fraction. The skewed scattering profile of the less dense sperm nuclei is due to insufficient protamine. Insufficient protamine affects DNA packing in reconstituted protamine-DNA assemblies differently from sperm nuclei Reconstituted assemblies with only 90% of the protamine necessary to neutralize DNA show a scattering profile that simply shifts the scattering peak to larger interhelical distances rather than skewing the scattering profile. We hypothesize that protamines can equilibrate throughout a reconstituted condensate, but not in sperm nuclei. This would suggest that the DNA in sperm nuclei is organized into discrete domains that prevent protamine equilibration. The (101) reflection is a combination of interaxial and helical repeat scattering. Its amplitude strongly depends on the correlation of phosphates on adjacent helices. There is a distinct difference in the intensities of the (101)reflections relative to the main interaxial reflection between reconstituted assemblies and sperm nuclei. The relative loss of intensity of the (101) reflection with nuclei is consistent with the suspected toroidal packing of DNA in sperm nuclei. Toroidal DNA is strongly curved, disrupting phosphate-phosphate correlation. These suspected toroids may also be the domains that hinder the equilibration of protamine throughout the nucleus. We are probing a possible domain structure using nuclease digestion. Protamines are initially serine phosphorylated when replacing histones on DNA. About 2-5 % of salmon protamines isolated from sperm are still phosphorylated. Incomplete dephosphorylation has been linked to increased DNA damage. We have previously found that serine phosphorylation of synthetic arginine peptides greatly reduces the attraction between helices; far more than would be expected based on a simple reduction in net charge. Protamines can be partially phosphorylated with protein kinase A. We find that protamine phosphorylation does dramatically decrease the attraction between helices. Even modest phosphorylation that reduces the protamine charge by only 5% increases the volume accessible to oxidizing species by 50%. Our direct measurement of forces between DNA helices has shown that water structuring dominates interactions at close distances. These hydration forces show two components: a longer ranged exponential force with decay length 0.5 nm that is due to the direct interaction of the hydration structure on one helix with that on a neighboring helix. This force can be either repulsive or attractive depending on the extent of complementarity of water structuring on the two helices. A second always repulsive exponential force with half the decay length is the hydration force equivalent of electrostatic image charge repulsion. The force amplitudes necessarily reflect not only the hydration of DNA itself but also the water structuring around DNA condensed counterions. We have previously parsed the amino acid contributions to the packing density of protamine-DNA assemblies. We uncovered quite simple rules that govern force amplitudes. Not surprisingly, the long range attraction increases with number of arginines in the peptide, while the short range repulsion is only slightly affected. In contrast the inclusion of neutral amino acids increases the short range repulsion while minimally affecting the attraction. We postulated that the neutral amino acids displaced water from the DNA without significantly affecting the arginine-DNA phosphate attraction. This displaced water would increase the hydration image-like repulsion. We have now investigated a set of homologous mono- and di-valent alkyl amine counterions in order to further connect hydration and force amplitudes. The addition of the first methyl group to ammonium (H3N-CH3+) increases the long range repulsion without much effect on the hydration image-like repulsion. This substitution reduces the number of hydrogen donors and reduces hydration of the ion. Adding a second alkyl carbon to the first (H3N+-CH2-CH3) now has almost no effect on the long range repulsion, but greatly increases the short range, half-decay length repulsion. The addition of another carbon group (H3N+-(CH22-CH3) follows the same trend. The number of hydrogen bond donors remains constant, but waters are displaced from DNA by the alkyl groups increasing the image-like repulsion. Adding methyl groups directly to the nitrogen (H2N+(CH3)2 and N+(CH3)4) both reduces the number of hydrogen bond donors and, therefore, water structuring around these ions and displaces water from DNA. Both force amplitudes significantly. While the mono-valent alkyl amines followed the trend expected from the arginine-neutral amino acid series, the di-valent alkyl amines show quite different behavior. We investigated the series +NH2-(CH2)M-NH2+ for M ranging from 2 to 5. The M = 4 and 5 diamines are the biogenic amines, putrescine and cadaverine, respectively. In this case the alkyl linker length has no effect on the short range half-decay length force, but the repulsive amplitude of the longer ranged force increases linearly with linker length. The difference in the effect of alkyl groups between mono- and di- amines illustrates that force amplitudes depend sensitively on the not only on the chemical nature of the counterion but also on the binding mode, i.e., territorial, phosphate, or groove. In collaboration with Alex Evilevitch we have uncovered a novel transition to a more fluid-like state of DNA tightly packed in both the bacteriophage lambda and the human Herpes simplex virus type 1. Since a similar transition is not seen for DNA condensed from bulk solution, we postulate that the DNA bending energy from being condensed within a spherical protein capsid drives the transition. The transition occurs at about 35oC for both viruses, close to the natural temperature for infection. The more fluid-like state of the DNA after the transition would make ejection of DNA into the target cell easier.